Herpes gestationis (HG) is a subepidermal bullous dermatosis of pregnancy characterized immunopathologically by circulating and tissue-bound IgG directed against an epidermal basement membrane zone (BMZ) antigen. It has been proposed that HG is related to bullous pemphigoid, another blistering dermatosis occurring in elderly patients, based on similar morphologic, histologic and immunofluorescence features. Both are strongly suspected to be autoimmune diseases, mediated by circulating anti-BMZ autoantibodies. The overall goals of the present study are to lay a groundwork characterizing the fundamental autoimmune components--the antigens and antibodies--of HG, comparing them to BP antigen/antibody systems, and to establish the pathogenic significance of the HG autoantibodies. More specifically, we intend to characterize biochemically and immunologically the epithelial antigens which may play a role in the pathogenesis of HG by Western immunoblotting, peptide mapping, determination of their solubilities, carbohydrate content and isoelectric points. Extra- versus intracellular location of the antigen will be evaluated using immunofluorescence techniques and ultrastructural localization will be determined by immuno-electron microscopy. Production of monoclonal and polyclonal antibodies will help clarify localization of relevant antigens identified by biochemical techniques. We also will further characterize the nature of the antibody response in HG by determining the IgG subclasses present in sera and skin using subclass specific monclonal antibodies for immunofluorescence studies. The findings will be compared to those of BP, to establish the similarities and differences in both antigen and antibody systems in these two autoimmune diseases. Finally, we intend to develop an animal model for HG by passive transfer of autoantibodies. This would provide evidence that the autoantibodies are in fact pathogenic, and would allow further investigation into the basic disease mechanisms, pathophysiology and the intriguing role which hormones play in development of autoimmune disease.